登録情報 データベース : EMDB / ID : EMD-62594 ダウンロードとリンクタイトル A Cryo_EM structure of 5_HT1A complex with TMT マップデータ 詳細 試料複合体 : A cryo_EM structure 5-HT1A complex with TMTタンパク質・ペプチド : Guanine nucleotide-binding protein G(i) subunit alpha-1タンパク質・ペプチド : Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1タンパク質・ペプチド : SCFV16タンパク質・ペプチド : Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2タンパク質・ペプチド : 5-hydroxytryptamine receptor 1Aリガンド : Cinobufotenineリガンド : [(2R)-1-[oxidanyl-[(2R,3R,5S,6R)-2,3,5,6-tetrakis(oxidanyl)-4-phosphonooxy-cyclohexyl]oxy-phosphoryl]oxy-3-tetradecanoyloxy-propan-2-yl] (5E,8E)-hexadeca-5,8,11,14-tetraenoateリガンド : GLYCOCHENODEOXYCHOLIC ACIDリガンド : CHOLESTEROLリガンド : water 残り2件を表示 表示を減らす 詳細 キーワード GPCR / 5_HT1A / MEMBRANE PROTEIN機能・相同性 機能・相同性情報分子機能 ドメイン・相同性 構成要素
regulation of serotonin secretion / Gi/o-coupled serotonin receptor activity / regulation of hormone secretion / regulation of dopamine metabolic process / regulation of behavior / receptor-receptor interaction / Serotonin receptors / G protein-coupled serotonin receptor activity / serotonin receptor signaling pathway / serotonin metabolic process ... regulation of serotonin secretion / Gi/o-coupled serotonin receptor activity / regulation of hormone secretion / regulation of dopamine metabolic process / regulation of behavior / receptor-receptor interaction / Serotonin receptors / G protein-coupled serotonin receptor activity / serotonin receptor signaling pathway / serotonin metabolic process / serotonin binding / neurotransmitter receptor activity / exploration behavior / behavioral fear response / regulation of vasoconstriction / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / regulation of eating behavior / adenylate cyclase inhibitor activity / T cell migration / positive regulation of protein localization to cell cortex / positive regulation of relaxation of smooth muscle / Adenylate cyclase inhibitory pathway / D2 dopamine receptor binding / adenylate cyclase-inhibiting dopamine receptor signaling pathway / adenylate cyclase-inhibiting serotonin receptor signaling pathway / G protein-coupled serotonin receptor binding / regulation of G protein-coupled receptor signaling pathway / cellular response to forskolin / regulation of mitotic spindle organization / mast cell degranulation / chemokine-mediated signaling pathway / establishment of mitotic spindle orientation / neuropeptide signaling pathway / Regulation of insulin secretion / response to prostaglandin E / positive regulation of cholesterol biosynthetic process / G protein-coupled receptor binding / response to peptide hormone / G-protein beta/gamma-subunit complex binding / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / Olfactory Signaling Pathway / Activation of the phototransduction cascade / G protein-coupled acetylcholine receptor signaling pathway / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / G-protein activation / Glucagon signaling in metabolic regulation / G beta:gamma signalling through CDC42 / Prostacyclin signalling through prostacyclin receptor / GDP binding / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / photoreceptor disc membrane / G beta:gamma signalling through BTK / ADP signalling through P2Y purinoceptor 12 / Sensory perception of sweet, bitter, and umami (glutamate) taste / Glucagon-type ligand receptors / Adrenaline,noradrenaline inhibits insulin secretion / Vasopressin regulates renal water homeostasis via Aquaporins / G alpha (z) signalling events / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / ADP signalling through P2Y purinoceptor 1 / cellular response to catecholamine stimulus / G beta:gamma signalling through PI3Kgamma / ADORA2B mediated anti-inflammatory cytokines production / adenylate cyclase-activating dopamine receptor signaling pathway / cellular response to prostaglandin E stimulus / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / GPER1 signaling / heterotrimeric G-protein complex / G alpha (12/13) signalling events / Inactivation, recovery and regulation of the phototransduction cascade / G-protein beta-subunit binding / extracellular vesicle / Thrombin signalling through proteinase activated receptors (PARs) / adenylate cyclase-activating G protein-coupled receptor signaling pathway / signaling receptor complex adaptor activity / spindle pole / ciliary basal body / GTPase binding / midbody / chemical synaptic transmission / G protein activity / cell cortex / Ca2+ pathway / High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells / G alpha (i) signalling events / G alpha (s) signalling events / G alpha (q) signalling events / cell division / 加水分解酵素; 酸無水物に作用; GTPに作用・細胞または細胞小器官の運動に関与 / cytoplasmic side of plasma membrane / Ras protein signal transduction / Extra-nuclear estrogen signaling / G protein-coupled receptor signaling pathway / lysosomal membrane / centrosome 類似検索 - 分子機能 5-Hydroxytryptamine 1A receptor / 5-hydroxytryptamine receptor family / G-protein alpha subunit, group I / Serpentine type 7TM GPCR chemoreceptor Srsx / G protein alpha subunit, helical insertion / G protein alpha subunit / Guanine nucleotide binding protein (G-protein), alpha subunit / G-protein alpha subunit / G-alpha domain profile. / G-protein, gamma subunit ... 5-Hydroxytryptamine 1A receptor / 5-hydroxytryptamine receptor family / G-protein alpha subunit, group I / Serpentine type 7TM GPCR chemoreceptor Srsx / G protein alpha subunit, helical insertion / G protein alpha subunit / Guanine nucleotide binding protein (G-protein), alpha subunit / G-protein alpha subunit / G-alpha domain profile. / G-protein, gamma subunit / G-protein gamma subunit domain profile. / G-protein gamma-like domain / G-protein gamma-like domain superfamily / GGL domain / G protein gamma subunit-like motifs / GGL domain / Guanine nucleotide-binding protein, beta subunit / G protein beta WD-40 repeat protein / G-protein, beta subunit / G-protein coupled receptors family 1 signature. / 7 transmembrane receptor (rhodopsin family) / G protein-coupled receptor, rhodopsin-like / GPCR, rhodopsin-like, 7TM / G-protein coupled receptors family 1 profile. / G-protein beta WD-40 repeat / WD40 repeat, conserved site / Trp-Asp (WD) repeats signature. / Trp-Asp (WD) repeats profile. / Trp-Asp (WD) repeats circular profile. / WD40 repeats / WD40 repeat / WD40-repeat-containing domain superfamily / WD40/YVTN repeat-like-containing domain superfamily / P-loop containing nucleoside triphosphate hydrolase 類似検索 - ドメイン・相同性 5-hydroxytryptamine receptor 1A / Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 / Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 / Guanine nucleotide-binding protein G(i) subunit alpha-1 類似検索 - 構成要素生物種 Homo sapiens (ヒト)手法 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度 : 2.59 Å 詳細 データ登録者Yuan Q / Li S 資金援助 中国, 1件 詳細 詳細を隠すOrganization Grant number 国 National Natural Science Foundation of China (NSFC) 中国
引用ジャーナル : Research (Wash D C) / 年 : 2025タイトル : Structural Pharmacology of Bufotenine Derivatives in Activating the 5-HT Receptor for Therapeutic Potential in Depression and Anxiety.著者 : Shu-Jie Li / Qing-Ning Yuan / Wen-Yuan Wu / Zhi-Han Chen / Duo Chen / Hong Shan / Qin-Yu Chu / Wen Hu / Kai Wu / Tao Liu / Yu-Yu Zhu / Li Hou / Jing Zhou / Jia Duan / Jin-Ao Duan / H Eric Xu / Hong-Yue Ma / 要旨 : The 5-HT receptor is a critical target in the treatment of depression and anxiety. Bufotenine derivatives, such as 5-methoxy-,-dimethyltryptamine (5-MeO-DMT), 5-hydroxy-,-dimethyltryptamine (5-OH-DMT) ... The 5-HT receptor is a critical target in the treatment of depression and anxiety. Bufotenine derivatives, such as 5-methoxy-,-dimethyltryptamine (5-MeO-DMT), 5-hydroxy-,-dimethyltryptamine (5-OH-DMT), and 5-hydroxy-,,-dimethyltryptamine-derived from traditional Chinese medicine-have shown antidepressant potential. However, the structural basis of their interaction with 5-HT and their pharmacological profiles remain incompletely understood. This study investigated bufotenine derivatives acting on multiple serotonin receptors, highlighting 5-HT as a key mediator of antidepressant effects while recognizing 5-HT as primarily responsible for hallucinogenic outcomes, to identify candidates with therapeutic efficacy but reduced hallucinogenic liability. We determined the cryo-electron microscopy structures of 5-HT bound to selected bufotenine derivatives. Functional assays in mice, including behavioral tests and receptor activation studies, were used to evaluate the antidepressant of each compound. Structural analysis revealed that all bufotenine derivatives engage conserved motifs within the 5-HT binding pocket, with 5-OH-DMT displaying a distinct interaction pattern. Behavioral assays showed that 5-OH-DMT and 5-MeO-DMT retained strong antidepressant and anxiolytic effects. These pharmacological differences correlate with their unique receptor binding conformation. This study delineated the structural pharmacology of bufotenine derivatives at the 5-HT receptor, identifying 5-OH-DMT and 5-MeO-DMT as promising antidepressant and anxiolytic candidates. The findings establish a molecular framework for the development of next-generation nonhallucinogenic therapeutics aimed at 5-HT. 履歴 登録 2024年12月5日 - ヘッダ(付随情報) 公開 2025年12月3日 - マップ公開 2025年12月3日 - 更新 2026年6月17日 - 現状 2026年6月17日 処理サイト : PDBc / 状態 : 公開
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